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Cell Envelope Homeostasis in Bacillus subtilis

枯草芽孢杆菌的细胞包膜稳态

基本信息

批准号：
10335184
负责人：
DAVID Z RUDNER
金额：
$ 34.7万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10335184
关键词：
ATP-Binding Cassette Transporters Address Antibiotic Therapy Antibiotics Area Bacillus subtilis Bacteria Binding Biochemical Biogenesis Cell Wall Cells Complement Complex Data Deacetylase Defect Development Ensure Extracellular Domain Genes Genetic Transcription Gram-Positive Bacteria Grant Growth Homeostasis Hydrolase Hydrolysis Infection Knowledge Link LytA enzyme Membrane Membrane Proteins Modeling Monitor Mutation N-Acetylmuramoyl-L-alanine Amidase Pathogenesis Pathway interactions Peptidoglycan Play Polymers Polysaccharides Process Proteolysis Regulation Regulatory Pathway Research Rod Role Sigma Factor Signal Pathway Signal Transduction Stress Surface Therapeutic Intervention Vaccine Therapy antimicrobial biological adaptation to stress cell envelope cell growth crosslink environmental stressor genetic analysis novel response transcription factor

项目摘要

PROJECT SUMMARY Bacteria are surrounded by a cell envelope that is essential for growth, integrity, and pathogenesis. The envelope and the biogenesis pathways that build it are also the target of many of our most effective antibiotic and vaccine therapies. Because cell envelope biogenesis has been such a successful target, it has been an active area of research for over half a century. Most of the genes responsible for the synthesis and remodeling of the different surface polymers have been identified and their biochemical activities characterized. However, our understanding of how these different assembly pathways are regulated and coordinated with each other during growth remains limited. This proposal focuses on two outstanding questions related to how bacteria coordinate envelope assembly, both principally focused on the cell wall peptidoglycan (PG). Cell growth requires PG synthesis but also the activity of cell wall hydrolases to allow expansion of the PG meshwork. How these potentially lytic enzymes are regulated and coordinated with growth remains an unanswered question in all bacteria. The first two aims of this proposal focus on how the model gram-positive bacterium Bacillus subtilis regulates two functionally redundant cell wall hydrolases and how it coordinates their activities with cell wall synthesis and envelope expansion. The third aim focuses on how cells sense and respond to perturbations to cell wall biogenesis. The σM-signaling pathway was identified over two decades ago as a stress-response pathway that is induced upon environmental stresses, including cell wall targeting antibiotics. This pathway is active at intermediate levels during unperturbed growth and functions in cell envelope homeostasis, monitoring envelope assembly and adjusting flux through the PG biogenesis pathway. What this pathway senses and how it transduces this information across the membrane have remained mysterious. The results of the proposed studies will elucidate critical regulatory pathways in envelope biogenesis and will inform the development of new treatments for infections. The Specific Aims of this application are: Aim 1: Elucidate how cells sense and respond to the extent of PG crosslinking to ensure proper expansion of the cell wall. Aim 2 Investigate how cell wall hydrolysis is coordinated with cell wall synthesis during growth. Aim 3: Determine how cells sense and respond to perturbations to cell envelope biogenesis.

项目总结

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High-Throughput Imaging of Bacillus subtilis.

DOI：
10.1007/978-1-0716-2221-6_19
发表时间：
2022
期刊：
Methods in molecular biology
影响因子：
0
作者：
Paula Montero Llopis;Ryan Stephansky;Xindan Wang
通讯作者：
Paula Montero Llopis;Ryan Stephansky;Xindan Wang

Intrinsically disordered protein regions are required for cell wall homeostasis in Bacillus subtilis.

DOI：
10.1101/gad.349895.122
发表时间：
2022-09-01
期刊：
GENES & DEVELOPMENT
影响因子：
10.5
作者：
Brunet, Yannick R. R.;Habib, Cameron;Brogan, Anna P. P.;Artzi, Lior;Rudner, David Z. Z.
通讯作者：
Rudner, David Z. Z.

XerD unloads bacterial SMC complexes at the replication terminus.

DOI：
10.1016/j.molcel.2020.12.027
发表时间：
2021-02-18
期刊：
Molecular cell
影响因子：
16
作者：
Karaboja X;Ren Z;Brandão HB;Paul P;Rudner DZ;Wang X
通讯作者：
Wang X

Dormant spores sense amino acids through the B subunits of their germination receptors.

DOI：
10.1038/s41467-021-27235-2
发表时间：
2021-11-25
期刊：
Nature communications
影响因子：
16.6
作者：
Artzi L;Alon A;Brock KP;Green AG;Tam A;Ramírez-Guadiana FH;Marks D;Kruse A;Rudner DZ
通讯作者：
Rudner DZ

Two broadly conserved families of polyprenyl-phosphate transporters.